The pulmonary artery response to hypoxia regulates gas exchange in normal lungs and may contribute to pulmonary hypertension in chronic lung disease. Endothelial cells play a key role in regulating pulmonary vascular responses to hypoxia through the action of vasodilator (EDRF-NO prostacyclin) and, as yet, unidentified vasoconstrictor (EDCF) factor(s). The contribution of these factors to the hypoxic response appears to be determined by artery location and also by the degree and duration of the hypoxic exposure. However, the mechanisms underlying hypoxic modulation of endothelial:smooth muscle cell interactions are unknown. The present study will employ spectrofluorometric analysis of calcium mobilization in isolated endothelial and smooth muscle cells, isometric tension recording of arterial contractility and bioassay techniques to determine: 1) the effect of moderate and severe hypoxia on activation of endothelial cells from different locations in pulmonary vascular tree, 2) the mechanisms underlying the endothelial response to hypoxia, 3) the mechanisms underlying hypoxic modulation of endothelial-smooth muscle cell interaction.